Imaging cAMP-specific phosphodiesterase-4 in human brain with R-[11C]rolipram and positron emission tomography. 2002

Jean N DaSilva, and Celia M Lourenco, and Jeffrey H Meyer, and Douglas Hussey, and William Z Potter, and Sylvain Houle
PET Centre, Centre for Addiction and Mental Health, University of Toronto, 250 College Street, Toronto, Ontario, Canada, M5T 1R8. jdasilva@ottawaheart.ca

Evidence of disruptions in cAMP-mediated signaling in several neuropsychiatric disorders has led to the development of R-[(11)C]rolipram for imaging phosphodiesterase-4 (PDE4) enzymes with positron emission tomography (PET). The high-affinity PDE4 inhibitor rolipram was previously reported to have an antidepressant effect in humans. PDE4 is abundant in the brain, and it hydrolyzes cAMP produced following stimulation of various neurotransmitter systems. PDE4 is regulated by intracellular cAMP levels. This paper presents the first PET study of R-[(11)C]rolipram in living human brain. Consistent with the wide distribution of PDE4, high radioactivity retention was observed in all regions representing the gray matter. Rapid metabolism was observed, and kinetic analysis demonstrated that the data fit in a two-tissue compartment model. R-[(11)C]Rolipram is thus suitable for imaging PDE4 and possibly cAMP signal transduction in the living human brain with PET.

UI MeSH Term Description Entries
D008297 Male Males
D008657 Metabolic Clearance Rate Volume of biological fluid completely cleared of drug metabolites as measured in unit time. Elimination occurs as a result of metabolic processes in the kidney, liver, saliva, sweat, intestine, heart, brain, or other site. Total Body Clearance Rate,Clearance Rate, Metabolic,Clearance Rates, Metabolic,Metabolic Clearance Rates,Rate, Metabolic Clearance,Rates, Metabolic Clearance
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D002250 Carbon Radioisotopes Unstable isotopes of carbon that decay or disintegrate emitting radiation. C atoms with atomic weights 10, 11, and 14-16 are radioactive carbon isotopes. Radioisotopes, Carbon
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D014018 Tissue Distribution Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. Distribution, Tissue,Distributions, Tissue,Tissue Distributions

Related Publications

Jean N DaSilva, and Celia M Lourenco, and Jeffrey H Meyer, and Douglas Hussey, and William Z Potter, and Sylvain Houle
October 2012, Biological psychiatry,
Jean N DaSilva, and Celia M Lourenco, and Jeffrey H Meyer, and Douglas Hussey, and William Z Potter, and Sylvain Houle
January 2011, Current radiopharmaceuticals,
Jean N DaSilva, and Celia M Lourenco, and Jeffrey H Meyer, and Douglas Hussey, and William Z Potter, and Sylvain Houle
July 2019, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism,
Jean N DaSilva, and Celia M Lourenco, and Jeffrey H Meyer, and Douglas Hussey, and William Z Potter, and Sylvain Houle
July 2005, NeuroImage,
Jean N DaSilva, and Celia M Lourenco, and Jeffrey H Meyer, and Douglas Hussey, and William Z Potter, and Sylvain Houle
February 2011, NeuroImage,
Jean N DaSilva, and Celia M Lourenco, and Jeffrey H Meyer, and Douglas Hussey, and William Z Potter, and Sylvain Houle
January 1992, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism,
Jean N DaSilva, and Celia M Lourenco, and Jeffrey H Meyer, and Douglas Hussey, and William Z Potter, and Sylvain Houle
May 1995, Synapse (New York, N.Y.),
Jean N DaSilva, and Celia M Lourenco, and Jeffrey H Meyer, and Douglas Hussey, and William Z Potter, and Sylvain Houle
January 1991, Journal of nuclear medicine : official publication, Society of Nuclear Medicine,
Jean N DaSilva, and Celia M Lourenco, and Jeffrey H Meyer, and Douglas Hussey, and William Z Potter, and Sylvain Houle
November 2003, Orvosi hetilap,
Jean N DaSilva, and Celia M Lourenco, and Jeffrey H Meyer, and Douglas Hussey, and William Z Potter, and Sylvain Houle
January 1987, International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology,
Copied contents to your clipboard!